Protein disulfide isomerase and sulfhydryl-dependent pathways in platelet activation

被引:115
作者
Essex, DW
Li, MR
Miller, A
Feinman, RD
机构
[1] Suny Downstate Med Ctr, Dept Biochem, Brooklyn, NY 11203 USA
[2] Suny Downstate Med Ctr, Dept Med, Div Hematol Oncol, Brooklyn, NY 11203 USA
关键词
D O I
10.1021/bi002454e
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The inhibition of blood platelet aggregation and secretion was studied using covalent thiol reagents, maleimides, or mercuribenzoates, or using inhibitors of protein disulfide isomerase (PDI), bacitracin or antibodies to PDI. As expected, both types of inhibitors were effective against stimulation by normal physiologic stimuli. On the other hand, when stimulation was initiated with the peptide LSARLAF, that specifically activates the integrin alpha IIb beta3 (the fibrinogen receptor), the PDI inhibitors were without effect. LSARLAF-induced aggregation was, however, inhibited by the sulfhydryl reagents. To further investigate the role of sulfhydryl-containing proteins and alpha IIb beta3, platelets were labeled with membrane-impermeant sulfhydryl reagents. Nine bands were found labeled on gel electrophoresis. Two of the labeled bands were identified as alpha IIb and beta3. The conclusions are that while PDI is required for platelet aggregation and secretion, an additional sulfhydryl-dependent step or protein is also required. This latter reaction occurs at the level of alpha IIb beta3. In distinction to most literature reports, at least a subpopulation of alpha IIb beta3 contains free sulfhydryl groups, consistent with the possibility that it is a substrate for PDI or part of the sulfhydryl-dependent response.
引用
收藏
页码:6070 / 6075
页数:6
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